Prenatal exposure to pesticide mixtures and the placental transcriptome: Insights from trimester-specific, sex-specific and metabolite-scaled analyses in the SAWASDEE cohort.

We investigated the effect of exposure to pesticide mixtures during pregnancy on the placental transcriptome, to link these exposures and placental functions. The Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) enrolled pregnant farmworkers from Thailand (n = 248), who were primarily exposed to organophosphate (OP) and pyrethroid pesticides. We measured maternal urinary levels of six non-specific OP metabolites expressed as three summary measures (dimethylalkylphosphates (DMAP), diethylalkylphosphates (DEAP), and dialkylphosphates (DAP) and three pyrethroid metabolites (3-phenoxybenzoic acid (3-PBA), cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA, trans-DCCA) during early, middle, and late pregnancy, and adjusted for urine dilution using creatinine.

A Prospective Analysis of Per- and Polyfluoroalkyl Substances from Early Pregnancy to Delivery in the Atlanta African American Maternal-Child Cohort.

Background: Longitudinal trends in per- and polyfluoroalkyl substances (PFAS) serum concentrations across pregnancy have not been thoroughly examined, despite evidence linking prenatal PFAS exposures with adverse birth outcomes.

Objectives: We sought to characterize longitudinal PFAS concentrations across pregnancy and to examine the maternal-fetal transfer ratio among participants in a study of risk and protective factors for adverse birth outcomes among African Americans.

Methods: In the Atlanta African American Maternal-Child cohort (2014-2020), we quantified serum concentrations of four PFAS in 376 participants and an additional eight PFAS in a subset of 301 participants during early (8-14 weeks gestation) and late pregnancy (24-30 weeks gestation).

Relationships of mitochondrial DNA mutations and select clinical diagnoses in perinatally HIV- and ART-exposed uninfected children.

The prevalence of pathogenic mutations within mitochondrial (mt) DNA of youth who were perinatally exposed to HIV and ART but remained uninfected (YHEU) were assessed relative to phenotypic clinical indicators of mitochondrial dysfunction (MtD). This was a cross-sectional, nested case-control study. A total of 144 cases met at least one clinical MtD definition and were matched with up to two controls each (n = 287).

Association of per- and polyfluoroalkyl substances with the antioxidant bilirubin across pregnancy.

Background: In mechanistic and preliminary human studies, prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is associated with oxidative stress, a potential contributor to maternal liver disease. Bilirubin is an endogenous antioxidant abundant in the liver that may serve as a physiological modulator of oxidative stress in pregnant people. Hence, our objective was to estimate the association between repeated measures of PFAS and bilirubin during pregnancy.

Transcriptome- and DNA methylation-based cell-type deconvolutions produce similar estimates of differential gene expression and differential methylation.

Background: Changing cell-type proportions can confound studies of differential gene expression or DNA methylation (DNAm) from peripheral blood mononuclear cells (PBMCs). We examined how cell-type proportions derived from the transcriptome versus the methylome (DNAm) influence estimates of differentially expressed genes (DEGs) and differentially methylated positions (DMPs).

Methods: Transcriptome and DNAm data were obtained from PBMC RNA and DNA of Kenyan children (n = 8) before, during, and 6 weeks following uncomplicated malaria.

Differential impact of prenatal PTSD symptoms and preconception trauma exposure on placental and methylation.

Perinatal stress is associated with altered placental methylation, which plays a critical role in fetal development and infant outcomes. This proof-of-concept pilot study investigated the impact of lifetime trauma exposure and perinatal PTSD symptoms on epigenetic regulation of placenta glucocorticoid signaling genes ( and Lifetime trauma exposure and PTSD symptoms during pregnancy were assessed in a racially/ethnically diverse sample of pregnant women ( = 198). Participants were categorized into three groups: (1) No Trauma (-T); (2) Trauma, No Symptoms (T - S); and (3) Trauma and Symptoms (T + S).

Transcriptome- and DNA methylation-based cell-type deconvolutions produce similar estimates of differential gene expression and differential methylation.

Background: Changing cell-type proportions can confound studies of differential gene expression or DNA methylation (DNAm) from peripheral blood mononuclear cells (PBMCs). We examined how cell-type proportions derived from the transcriptome versus the methylome (DNAm) influence estimates of differentially expressed genes (DEGs) and differentially methylated positions (DMPs).

Methods: Transcriptome and DNAm data were obtained from PBMC RNA and DNA of Kenyan children (n = 8) before, during, and 6 weeks following uncomplicated malaria.

Examining the Biological Impacts of Parent-Child Relationship Dynamics on Preschool-Aged Children who have Experienced Adversity.

Parent-child relationship dynamics have been shown to predict socioemotional and behavioral outcomes for children, but little is known about how they may affect biological development. The aim of this study was to test if observational assessments of parent-child relationship dynamics (cohesion, enmeshment, and disengagement) were associated with three biological indices of early life adversity and downstream health risk: (1) methylation of the glucocorticoid receptor gene (), (2) telomere attrition, and (3) mitochondrial biogenesis, indexed by mitochondrial DNA copy number (mtDNAcn), all of which were measured in children's saliva. We tested hypotheses using a sample of 254 preschool-aged children ( age = 51.

Toward a more holistic approach to the study of exposures and child outcomes.

The current work was designed to demonstrate the application of the exposome framework in examining associations between exposures and children's long-term neurodevelopmental and behavioral outcomes. Longitudinal data were collected from birth through age 6 from 402 preterm infants. Three statistical methods were utilized to demonstrate the exposome framework: exposome-wide association study, cumulative exposure and machine learning models, with and without epigenetic data.

Epigenome-wide association study identifies neonatal DNA methylation associated with two-year attention problems in children born very preterm.

Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age.

Contributions of prenatal risk factors and neonatal epigenetics to cognitive outcome in children born very preterm.

Children born less than 30 weeks gestational age (GA) are at high risk for neurodevelopmental delay compared to term peers. Prenatal risk factors and neonatal epigenetics could help identify preterm children at highest risk for poor cognitive outcomes. We aimed to understand the associations among cumulative prenatal risk, neonatal DNA methylation, and child cognitive ability at age 3 years, including whether DNA methylation mediates the association between prenatal risk and cognitive ability.

Two-Year Autism Risk Screening and 3-Year Developmental Outcomes in Very Preterm Infants.

Importance: Use of the Modified Checklist for Autism in Toddlers, Revised With Follow-Up, a 2-stage parent-report autism risk screening tool, has been questioned due to reports of poor sensitivity and specificity. How this measure captures developmental delays for very preterm infants may provide support for continued use in pediatric care settings.

Objective: To determine whether autism risk screening with the 2-stage parent-report autism risk screening tool at age 2 years is associated with behavioral and developmental outcomes at age 3 in very preterm infants.

Epigenetic age acceleration, neonatal morbidities, and neurobehavioral profiles in infants born very preterm.

Epigenetic age acceleration is a risk factor for chronic diseases of ageing and may reflect aspects of biological ageing. However, few studies have examined epigenetic ageing during the early neonatal period in preterm infants, who are at heightened risk of developmental problems. We examined relationships between neonatal age acceleration, neonatal morbidities, and neurobehavioral domains among very preterm (<30 weeks gestation) infants to characterize whether infants with early morbidities or different neurobehavioral characteristics had accelerated or decelerated epigenetic ageing.

Neurodevelopmental and behavioral outcomes of very preterm infants: latent profile analysis in the Environmental influences on Child Health Outcomes (ECHO) Program.

Background: Very preterm infants are at high risk for neurodevelopmental impairments. We used a child-centered approach (latent profile analysis [LPA]) to describe 2-year neurobehavioral profiles for very preterm infants based on cognitive, motor, and behavioral outcomes. We hypothesized that distinct outcome profiles would differ in the severity and co-occurrence of neurodevelopmental and behavioral impairment.

Evaluation of pediatric epigenetic clocks across multiple tissues.

Background: Epigenetic clocks are promising tools for assessing biological age. We assessed the accuracy of pediatric epigenetic clocks in gestational and chronological age determination.

Results: Our study used data from seven tissue types on three DNA methylation profiling microarrays and found that the Knight and Bohlin clocks performed similarly for blood cells, while the Lee clock was superior for placental samples.

Sexually dimorphic methylation patterns characterize the placenta and blood from extremely preterm newborns.

Background: Health outcomes among children born prematurely are known to be sexually dimorphic, with male infants often more affected, yet the mechanism behind this observation is not clear. CpG methylation levels in the placenta and blood also differ by sex and are associated with adverse health outcomes. We contrasted CpG methylation levels in the placenta and neonatal blood (n = 358) from the Extremely Low Gestational Age Newborn (ELGAN) cohort based on the EPIC array, which assays over 850,000 CpG sites across the epigenome.

Newborn metabolomic signatures of maternal per- and polyfluoroalkyl substance exposure and reduced length of gestation.

Marginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. In the present study, we characterized the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot metabolome among 267 African American dyads in Atlanta, Georgia between 2016 and 2020.